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Lect 10 P450


Xenobiotic metabolizing enzymes have been grouped into 2 phases. What does each one contain? Phase I : Oxidation, reduction, and hydrolytic reactions .......... Phase II : conjugation reactions
What are phase I reactions carried out by? CYPs, Flavin-containing monoonxygenases (FMO) and Epoxide hydrolases (EH)
What is considered the major "Metabolic clearing house" for both endogenous chemicals, and Xenobiotics. The liver
Drugs that are orally administered are absorbed in the gut and taken to the liver through the _____ vein, where they undergo significant metabolism Portal
Where would you find xenobiotics metabolizing enzymes within the cell? intracellular membranes and cytosol
What is Heme The oxygen binding moiety found in hemoglobin
What does the heme contains that allow it to bind oxygen in the CYP active site Atom of iron in hydrocarbon cage
What does CYPs use to carry out the oxidation of substrate? O2 and H+
Metabolism of a substrate by a CYP consumes _____ molecule of molecular oxygen and produces an ______ and a ________ as a by product One, oxidized substrate, molecule of water
True/False: drug metabolizing CYPs and the CYPs that catalyze steroid and bile acids have very specific substrate preferences FALSE, only CYPs that catalyze steroid and bile acids have that
True/False: can can a single compound be metabolized by different CYPs at different rate? True, They can even metabolize a single molecule at different positions on the molecule
Generally, what is the half lives of drugs? What about endogenous compounds? Drugs 3-30 hours .. Endogenous compounds - seconds or minutes
What is one of the main reasons for the predominance of drug-drug interactions? The feature of extensive overlapping of substrate specificities of CYPs
What can inhibit the metabolism of some drugs leading to elevated plasma levels? 2 drugs competing for binding to an active site .. one or both of these drugs would be inhibited
What does a narrow therapeutic index for the drugs mean? unwanted toxicities
In naming CYPs what is the family, subfamily, and gene number . Example, CYP3A4 3- Family .. A-Subfamily .. 4- Gene number
What are the CYPs involved in the metabolism of Xenobiotics? There are 12 of them (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, and 3A5)
Where is the greatest amount of CYPs found? The liver, and then lower amount in the lung, kidney, and CNS
The expression of different CYPs can differ markedly as a result of: - Dietary and environmental exposure to inducers - Heritable polymorphic differences in gene structure - Tissue specific expression patterns
What are the most active CYPs for drug metabolism? Those found in CYP2C, CYP2D, CYP3A sub-family
Which CYP is most abundantly expressed in the liver and involved in the metabolism of over 50% clinically used drugs? CYP3A4
What are some CYPs that exhibit polymorphism? 2A6, 2C9, 2C19, 2D6
When does metabolism-related drug interactions occur? when 2 drugs are co administered and subjected to metabolism by the same enzyme
Created by: amiqnais



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